Cancer results when a vertebrate""s own cells become malignant. Healthy individuals at any given time carry potentially malignant cells in their body. These cells are generally recognized and killed by the individuals"" immune system. However, some malignant cells are not destroyed by the immune system and proliferate into tumors.
Currently, there are not adequate and specific therapies for cancer. For example, surgical excision of tumors is not an effective method of treatment where the cancer has metastasized. In addition, radiation and chemotherapy often kill normal cells in addition to cancerous cells.
Another problem is that chemotherapeutic agents follow first-order kinetics. As a result, a constant percentage, rather than a constant number of cells are killed by a given application of a chemotherapeutic agent. Consequently, malignant cells, which could cause a relapse in the disease, remain even when a patent is diagnosed as having complete clinical remission.
A method of suppressing cancer that employs the individual""s own immune system would be useful.
The present invention relates to Applicant""s finding that expression of the JE/MCP-1 protein in malignant cells suppresses their ability to form tumors in vivo. Thus, the invention comprises, in one embodiment, a method of suppressing tumor formation in a vertebrate by administering to the vertebrate a therapeutically effective amount of JE/MCP-1. The protein can be administered alone or as an adjuvant to surgery or cytotoxic chemotherapy.
The suppressive effect of JE/MCP-1 depends on the induction of the vertebrate""s immune response, specifically the response of monocytes. Thus, in another embodiment, the invention comprises a method of increasing a vertebrate""s monocyte-mediated tumoricidal activity in vivo by administering to the vertebrate an effective amount of JE/MCP-1.
JE/MCP-1 can also be administered to treat localized complications of malignancy. For example, JE/MCP-1 could be used to inhibit malignant pleural effusions or ascites. Therefore, in a further embodiment, the invention comprises methods of inhibiting pleural effusion or ascites in a vertebrate by locally administering JE/MCP-1 to the anatomic spaces between the lung and the pleural membrane or the stomach and the peritoneum.
In a further embodiment tumor killing cells, such as tumor infiltrating lymphocytes (TIL cells) are genetically engineered to express the JE/MCP-1 protein. The engineered cells therefore can be administered to a vertebrate to provide a synergistic local tumor cell killing.
In the alternative, any cell type which localizes to, or can be made to localize to a site of tumor formation can be genetically engineered to express JE/MCP-1 protein and used for gene therapy. Cells can be engineered in vivo, at the site of tumor formation, or they can be engineered Ad vitro, and subsequently administered to a vertebrate where they will express JE/MCP-1 at the site of tumor formation.
The presence of JE/MCP-1 in vivo is accompanied by a local increase in the presence of eosinophils. Therefore, another aspect of the subject invention comprises methods of combatting a parasitic infection in a vertebrate animal by administering to that vertebrate an effective amount of JE/MCP-1.
A major advantage of using JE/MCP-1 in treating cancer is that it employs the individual""s own immune system and therefore would have fewer side-effects than conventional chemotherapies. In addition, JE/MCP-1 stimulates monocytes and, as such, does not depend on a total immunologic response.